Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Secretory Phospholipase A2 (sPLA2) Isozymes as Potential Targets in Tobacco Condensate- induced Colon Damage

Author(s): Sanjeev K. Sharma*, Subodh K. Yadav, Ujjawal Sharma, Pramod Avti, Satyavati Rana and Krishan L. Khanduja*

Volume 23, Issue 4, 2023

Published on: 20 August, 2022

Page: [450 - 460] Pages: 11

DOI: 10.2174/1871520622666220527094219

Price: $65

Abstract

Aims: To find out the role of secretory phospholipase A2 (sPLA2) isozymes as potential targets in tobacco condensate-induced colon damage.

Background: The effects of cigarette smoke condensate (CSC) and the molecular mechanisms involved in the regulation of phospholipase A2 (PLA2) and its isozymes in colon cells, which are still unclear and emerging, are studied.

Objectives: The study aimed to check the effect of CSC on cell viability and reactive oxygen species (ROS) and superoxide. Also, the effect of CSC on gene expression of different secretory phospholipase A2 (sPLA2) was evaluated. Moreover, the impact of inhibition of sPLA2 on various cell properties i.e. cell viability, cell proliferation, membrane damage and free radicals’ generation is also studied.

Methods: CSC-induced changes were evaluated in cell viability by MTT assay, followed by the evaluation of membrane modulation by flow cytometry, free radical generation by fluorescent dyes, PLA2 isoforms gene expression patterns and their suppression by small interfering RNA (siRNA) studied in HCT-15 male and HT-29 female colon cells.

Results: Our results demonstrate that HCT-15 and HT-29 cells treated with CSC significantly reduced the cell viability by 50% within 48 h and significantly enhanced the total reactive oxygen species (ROS) by 2 to 10-fold, and mitochondrial ROS (mtROS) and superoxide radicals (SOR) by 2-fold each. Treatment with CSC significantly unregulated secretory phospholipase A2 (sPLA2) IID group and down-regulated IB and cytosolic phospholipase (cPLA2) IVA groups in HCT-15 cells without affecting them in HT-29 cells. Silencing the sPLA2 IID group results in an increase in cell viability and a decrease in ROS. Silencing the PLA2 IVA gene in the HCT-15 cells showed a reduced expression which had no impact on the CSC-induced cell proliferation, membrane damage and free radicals (ROS, mtROS, and SOR) generation.

Conclusion: Therefore, identifying cell-specific sPLA2 isozymes seems to play a key role in controlling the ROSinduced damage by CSC and helps develop specific therapeutic strategies.

Keywords: Cigarette smoke condensate, colon cancer cells, phospholipase A2 isozymes, reactive oxygen species (ROS), small-interfering ribonucleic acid (siRNA), therapeutic target.

« Previous Next »
Graphical Abstract

[1]
WHO Report on the Global Tobacco Epidemic 2011. Available from: http://www.who.int/tobacco/global_report/2011/en/
[2]
Chao, A.; Thun, M.J.; Jacobs, E.J.; Henley, S.J.; Rodriguez, C.; Calle, E.E. Cigarette smoking and colorectal cancer mortality in the cancer prevention study II. J. Natl. Cancer Inst., 2000, 92(23), 1888-1896.
[http://dx.doi.org/10.1093/jnci/92.23.1888] [PMID: 11106680]
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[4]
Arnold, M.; Sierra, M.S.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global patterns and trends in colorectal cancer incidence and mortality. Gut, 2017, 66(4), 683-691.
[http://dx.doi.org/10.1136/gutjnl-2015-310912] [PMID: 26818619]
[5]
Thrumurthy, S.G.; Thrumurthy, S.S.; Gilbert, C.E.; Ross, P.; Haji, A. Colorectal adenocarcinoma: Risks, prevention and diagnosis. BMJ, 2016, 354, i3590.
[http://dx.doi.org/10.1136/bmj.i3590] [PMID: 27418368]
[6]
Hannan, L.M.; Jacobs, E.J.; Thun, M.J. The association between cigarette smoking and risk of colorectal cancer in a large prospective cohort from the United States. Cancer Epidemiol. Biomarkers Prev., 2009, 18(12), 3362-3367.
[http://dx.doi.org/10.1158/1055-9965.EPI-09-0661] [PMID: 19959683]
[7]
Limsui, D.; Vierkant, R.A.; Tillmans, L.S.; Wang, A.H.; Weisenberger, D.J.; Laird, P.W.; Lynch, C.F.; Anderson, K.E.; French, A.J.; Haile, R.W.; Harnack, L.J.; Potter, J.D.; Slager, S.L.; Smyrk, T.C.; Thibodeau, S.N.; Cerhan, J.R.; Limburg, P.J. Cigarette smoking and colorectal cancer risk by molecularly defined subtypes. J. Natl. Cancer Inst., 2010, 102(14), 1012-1022.
[http://dx.doi.org/10.1093/jnci/djq201] [PMID: 20587792]
[8]
Huang, Y.M.; Wei, P.L.; Ho, C.H.; Yeh, C.C. Cigarette smoking associated with colorectal cancer survival: A nationwide, population-based cohort study. J. Clin. Med., 2022, 11(4), 913.
[http://dx.doi.org/10.3390/jcm11040913] [PMID: 35207186]
[9]
Parajuli, R.; Bjerkaas, E.; Tverdal, A.; Selmer, R.; Le Marchand, L.; Weiderpass, E.; Gram, I.T. The increased risk of colon cancer due to cigarette smoking may be greater in women than men. Cancer Epidemiol. Biomarkers Prev., 2013, 22(5), 862-871.
[http://dx.doi.org/10.1158/1055-9965.EPI-12-1351] [PMID: 23632818]
[10]
Rodgman, A.; Perfetti, T.A. The chemical components of tobacco and tobacco smoke; USA CRC Press Boca.Ranton, 2013.
[11]
Stinn, W.; Arts, J.H.; Buettner, A.; Duistermaat, E.; Janssens, K.; Kuper, C.F.; Haussmann, H.J. Murine lung tumor response after expo-sure to cigarette mainstream smoke or its particulate and gas/vapor phase fractions. Toxicology, 2010, 275(1-3), 10-20.
[http://dx.doi.org/10.1016/j.tox.2010.05.005] [PMID: 20594951]
[12]
Hecht, S.S. Lung carcinogenesis by tobacco smoke. Int. J. Cancer, 2012, 131(12), 2724-2732.
[http://dx.doi.org/10.1002/ijc.27816] [PMID: 22945513]
[13]
Hoffmann, D.; Hoffmann, I. The changing cigarette, 1950-1995. J. Toxicol. Environ. Health, 1997, 50(4), 307-364.
[http://dx.doi.org/10.1080/009841097160393] [PMID: 9120872]
[14]
Talhout, R.; Schulz, T.; Florek, E.; van Benthem, J.; Wester, P.; Opperhuizen, A. Hazardous compounds in tobacco smoke. Int. J. Environ. Res. Public Health, 2011, 8(2), 613-628.
[http://dx.doi.org/10.3390/ijerph8020613] [PMID: 21556207]
[15]
Adibhatla, M.R.; Hatcher, J.F. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic. Biol. Med., 2006, 40(3), 376-387.
[http://dx.doi.org/10.1016/j.freeradbiomed.2005.08.044] [PMID: 16443152]
[16]
Murakami, M.; Sato, H.; Taketomi, Y.; Yamamoto, K. Integrated lipidomics in the secreted phospholipase A2 biology. Int. J. Mol. Sci., 2011, 12(3), 1474-1495.
[http://dx.doi.org/10.3390/ijms12031474] [PMID: 21673902]
[17]
Kudo, I.; Murakami, M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat., 2002, 68-69, 3-58.
[http://dx.doi.org/10.1016/S0090-6980(02)00020-5] [PMID: 12432908]
[18]
Steiner, M.R.; Clark, M.A.; Bomalaski, J.S. Inhibitors of phospholipase A2 and eicosanoid biosynthesis in cancer. Drug News Perspect., 1994, 7, 344-351.
[19]
Cheng, S.E.; Luo, S.F.; Jou, M.J.; Lin, C.C.; Kou, Y.R.; Lee, I.T.; Hsieh, H.L.; Yang, C.M. Cigarette smoke extract induces cytosolic phos-pholipase A2 expression via NADPH oxidase, MAPKs, AP-1, and NF-kappaB in human tracheal smooth muscle cells. Free Radic. Biol. Med., 2009, 46(7), 948-960.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.01.006] [PMID: 19280714]
[20]
Tselepis, A.D.; Panagiotakos, D.B.; Pitsavos, C.; Tellis, C.C.; Chrysohoou, C.; Stefanadis, C. Smoking induces lipoprotein-associated phospholipase A2 in cardiovascular disease free adults: The ATTICA Study. Atherosclerosis, 2009, 206(1), 303-308.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.02.016] [PMID: 19394616]
[21]
Kleber, M.E.; Siekmeier, R.; Delgado, G.; Grammer, T.B.; Winkelmann, B.R.; Scharnagl, H.; Boehm, B.O.; März, W. C-reactive protein and lipoprotein-associated phospholipase A2 in smokers and nonsmokers of the Ludwigshafen risk and cardiovascular health study. Adv. Exp. Med. Biol., 2015, 832, 15-23.
[http://dx.doi.org/10.1007/5584_2014_6] [PMID: 25300684]
[22]
Yadav, S.K.; Sharma, S.K.; Farooque, A.; Kaushik, G.; Kaur, B.; Pathak, C.M.; Dwarakanath, B.S.; Khanduja, K.L. Cytosolic phospho-lipase A2 (cPLA2) IVA as a potential signature molecule in cigarette smoke condensate induced pathologies in alveolar epithelial lineages. Lipids Health Dis., 2016, 15(1), 129.
[http://dx.doi.org/10.1186/s12944-016-0300-x] [PMID: 27528014]
[23]
Kumar, S.; Sharma, S.K.; Kaushik, G.; Avti, P.K.; Pandey, S.K.; Sarma, P.; Medhi, B.; Khanduja, K.L. Therapeutic potential of arachidonyl trifluromethyl ketone, a cytosolic phospholipaseA2 IVA specific inhibitor, in cigarette smoke condensate-induced pathological conditions in alveolar type I & II epithelial cells. Toxicol. In Vitro, 2019, 54, 215-223.
[http://dx.doi.org/10.1016/j.tiv.2018.09.013] [PMID: 30253184]
[24]
Kaushik, G.; Kaushik, T.; Khanduja, S.; Pathak, C.M.; Khanduja, K.L. Cigarette smoke condensate promotes cell proliferation through disturbance in cellular redox homeostasis of transformed lung epithelial type-II cells. Cancer Lett., 2008, 270(1), 120-131.
[http://dx.doi.org/10.1016/j.canlet.2008.04.039] [PMID: 18550274]
[25]
Sharma, U.; Pal, D.; Singh, S.K.; Kakkar, N.; Prasad, R. Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: Plausible role in tumorigenesis. Biochimie, 2014, 104, 27-35.
[http://dx.doi.org/10.1016/j.biochi.2014.05.011] [PMID: 24909115]
[26]
Yang, H.; Acker, J.; Chen, A.; McGann, L. In situ assessment of cell viability. Cell Transplant., 1998, 7(5), 443-451.
[http://dx.doi.org/10.1177/096368979800700503] [PMID: 9786064]
[27]
Wan, C.P.; Myung, E.; Lau, B.H. An automated micro-fluorometric assay for monitoring oxidative burst activity of phagocytes. J. Immunol. Methods, 1993, 159(1-2), 131-138.
[http://dx.doi.org/10.1016/0022-1759(93)90150-6] [PMID: 8445246]
[28]
Shi, G.Y.; Gao, F.; Shi, X.G.; Tang, X.M. Detection of cellular reactive oxygen species by flow cytometry. Shanghai Di-erYikeDaxueXuebao, 2001, 21, 122-134.
[29]
Sharma, U.; Pal, D.; Prasad, R. A novel role of alkaline phosphatase in the ERK1/2 dephosphorylation in renal cell carcinoma cell lines: A new plausible therapeutic target. Biochimie, 2014, 107(Pt B), 406-409.
[http://dx.doi.org/10.1016/j.biochi.2014.09.016] [PMID: 25241253]
[30]
Avti, P.K.; Kumar, S.; Pathak, C.M.; Vaiphei, K.; Khanduja, K.L. Smokeless tobacco impairs the antioxidant defense in liver, lung, and kidney of rats. Toxicol. Sci., 2006, 89(2), 547-553.
[http://dx.doi.org/10.1093/toxsci/kfj041] [PMID: 16280382]
[31]
Avti, P.K.; Vaiphei, K.; Pathak, C.M.; Khanduja, K.L. Involvement of various molecular events in cellular injury induced by smokeless tobacco. Chem. Res. Toxicol., 2010, 23(7), 1163-1174.
[http://dx.doi.org/10.1021/tx900458x] [PMID: 20521779]
[32]
Bombick, D.W.; Ayres, P.H.; Putnam, K.; Bombick, B.R.; Doolittle, D.J. Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 3. In vitro toxicity of whole smoke. Food Chem. Toxicol., 1998, 36(3), 191-197.
[http://dx.doi.org/10.1016/S0278-6915(97)00155-5] [PMID: 9609392]
[33]
Waldren, C.A.; Vannais, D.B.; Knowlton, M.S.; Domenico, K.K.; Smith, C.J.; Doolittle, D.J. The role of glutathione in the toxicity of smoke condensates from cigarettes that burn or heat tobacco. Free Radic. Biol. Med., 2001, 30(12), 1400-1406.
[http://dx.doi.org/10.1016/S0891-5849(01)00549-4] [PMID: 11390185]
[34]
Dennis, E.A.; Norris, P.C. Eicosanoid storm in infection and inflammation. Nat. Rev. Immunol., 2015, 15(8), 511-523.
[http://dx.doi.org/10.1038/nri3859] [PMID: 26139350]
[35]
Hurley, B.P.; McCormick, B.A. Multiple roles of phospholipase A2 during lung infection and inflammation. Infect. Immun., 2008, 76(6), 2259-2272.
[http://dx.doi.org/10.1128/IAI.00059-08] [PMID: 18411286]
[36]
Scott, K.F.; Sajinovic, M.; Hein, J.; Nixdorf, S.; Galettis, P.; Liauw, W.; de Souza, P.; Dong, Q.; Graham, G.G.; Russell, P.J. Emerging roles for phospholipase A2 enzymes in cancer. Biochimie, 2010, 92(6), 601-610.
[http://dx.doi.org/10.1016/j.biochi.2010.03.019] [PMID: 20362028]
[37]
Thommesen, L.; Sjursen, W.; Gåsvik, K.; Hanssen, W.; Brekke, O.L.; Skattebøl, L.; Holmeide, A.K.; Espevik, T.; Johansen, B.; Laegreid, A. Selective inhibitors of cytosolic or secretory phospholipase A2 block TNF-induced activation of transcription factor nuclear factor-kappa B and expression of ICAM-1. J. Immunol., 1998, 161(7), 3421-3430.
[PMID: 9759860]
[38]
Agarwal, A.R.; Yin, F.; Cadenas, E. Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells. Am. J. Respir. Cell Mol. Biol., 2014, 51(2), 284-293.
[http://dx.doi.org/10.1165/rcmb.2013-0523OC] [PMID: 24625219]
[39]
Ahmed, D.; Eide, P.W.; Eilertsen, I.A.; Danielsen, S.A.; Eknæs, M.; Hektoen, M.; Lind, G.E.; Lothe, R.A. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis, 2013, 2(9), e71.
[http://dx.doi.org/10.1038/oncsis.2013.35] [PMID: 24042735]
[40]
Kennedy, B.P.; Soravia, C.; Moffat, J.; Xia, L.; Hiruki, T.; Collins, S.; Gallinger, S.; Bapat, B. Overexpression of the nonpancreatic secreto-ry group II PLA2 messenger RNA and protein in colorectal adenomas from familial adenomatous polyposis patients. Cancer Res., 1998, 58(3), 500-503.
[PMID: 9458096]
[41]
Murakami, M.; Yoshihara, K.; Shimbara, S.; Sawada, M.; Inagaki, N.; Nagai, H.; Naito, M.; Tsuruo, T.; Moon, T.C.; Chang, H.W.; Kudo, I. Group IID heparin-binding secretory phospholipase A(2) is expressed in human colon carcinoma cells and human mast cells and up-regulated in mouse inflammatory tissues. Eur. J. Biochem., 2002, 269(11), 2698-2707.
[http://dx.doi.org/10.1046/j.1432-1033.2002.02938.x] [PMID: 12047378]
[42]
Nethery, D.; Callahan, L.A.; Stofan, D.; Mattera, R.; DiMarco, A.; Supinski, G. PLA(2) dependence of diaphragm mitochondrial formation of reactive oxygen species. J. Appl. Physiol., 2000, 89(1), 72-80.
[http://dx.doi.org/10.1152/jappl.2000.89.1.72] [PMID: 10904037]
[43]
Park, J.B.; Lee, C.S.; Jang, J.H.; Ghim, J.; Kim, Y.J.; You, S.; Hwang, D.; Suh, P.G.; Ryu, S.H. Phospholipase signalling networks in cancer. Nat. Rev. Cancer, 2012, 12(11), 782-792.
[http://dx.doi.org/10.1038/nrc3379] [PMID: 23076158]
[44]
Morioka, Y.; Ikeda, M.; Saiga, A.; Fujii, N.; Ishimoto, Y.; Arita, H.; Hanasaki, K. Potential role of group X secretory phospholipase A(2) in cyclooxygenase-2-dependent PGE(2) formation during colon tumorigenesis. FEBS Lett., 2000, 487(2), 262-266.
[http://dx.doi.org/10.1016/S0014-5793(00)02350-4] [PMID: 11150521]

Rights & Permissions Print Cite
Article Metrics
3
© 2024 Bentham Science Publishers | Privacy Policy